Mechanism for transforming growth factor beta and IL-2 enhancement of IgA expression in lipopolysaccharide-stimulated B cell cultures.
Transforming growth factor beta (TGF-beta), but not IL-2, causes LPS-stimulated surface (s)IgA- cells to express sIgA. Although there is a progression of sIgA- cells to sIgA+ cells and then to IgA-secreting cells, there is not a parallel change in ratio of membrane to secreted form of alpha-mRNA. In fact, the secreted form of alpha-mRNA is always the predominant form even before the expression of sIgA. However, at least some of the secreted alpha-mRNA transcripts are sterile. The increase in sIgA expression and the induction of sterile transcripts indicate that TGF-beta enhances H chain class switching to IgA as opposed to allowing the growth and maturation of cells precommitted to IgA secretion. The addition of IL-2 to cultures with TGF-beta results in a 5- to 10-fold increase in IgA secretion compared to cultures to which only TGF-beta was added. In these cultures IL-2 increases neither the proportion nor the total number of sIgA+ cells suggesting that IL-2 acts to increase IgA secretion. However, IL-2 does not cause a change in the ratio of secreted to membrane form of alpha-mRNA nor does it lead to an increase in the steady state level of alpha-mRNA comparable to the increase in secreted IgA. Thus, it appears that regulation of transcription of IgA as sIgA- cells proliferate and undergo H class switching and maturation does not follow the same sequence as is seen when sIgM+ cells proliferate and mature to Ig-secreting cells. Furthermore, the data suggest that maturation to high level secretion is controlled posttranscriptionally.
Lebman
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DNAX Research Institute, Palo Alto, CA 94304.
Lee
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Coffman
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D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000235:genetics; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D013997:Time Factors; D015291:Transforming Growth Factors / Q000494:pharmacology*
D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007376:Interleukin-2; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D015291:Transforming Growth Factors